The organization of cardiovascular regulatory mechanisms is not clearly understood at present. This lack of knowledge may be one of the reasons responsible for our incomplete understanding of mechanisms involved in some cardiovascular diseases. The long-term goals of this grant application for competitive renewal are to identify structures involved in cardiovascular regulation, delineate interconnections between these structures and characterize their function. A pharmacological approach will be used in an attempt to resolve these problems. Recently, discrete pressor and depressor areas have been identified in the ventrolateral medulla in this and other laboratories. Information regarding the role of various neurotransmitters in these regions is just beginning to be collected. We have studied the role of enkephalins, gamma aminobutyric acid and acetylcholine in these regions. These studies will be continued. Projections from the pressor area to the intermediolateral column of the spinal cord have been identified. The latter is the final common pathway from which innervation to the heart and blood vessels originates. Identification of the neurotransmitters/neuromodulators in the pathway between the medulla and the spinal cord is essential for our understanding of cardiovascular function in normal conditions. These studies will help in understanding neurochemical abnormalities in cardiovascular diseases and open new avenues for treating them. L-glutamate, which is known to stimulate only cell-bodies, will be microinjected into the various areas in the medulla and the spinal cord in order to identify areas with cardiovascular function. Then, putative neurotransmitters will be microinjected into the same areas and their cardiovascular actions characterized. Specific antagonists will be microinjected into the same sites in order to test the specificity of these responses. These pharmacological actions will then be confirmed by microiontophoretic studies on individual cardiovascular neurons. Anatomic connections between the cardiovascular areas in the medulla and the spinal cord will be investigated by the 14C-2-deoxyglucose method.